Psoas Muscle Area and Quality Are Independent Predictors of Survival in Patients Treated for Abdominal Aortic Aneurysms.

BACKGROUND: Sarcopenia is associated with mortality after abdominal aortic aneurysm (AAA) repair. The reliability of computed tomography (CT) core muscle areas and quality-that is, densities and their association with postoperative survival in patients undergoing AAA treatment-were retrospectively studied. METHODS: Psoas muscle area (PMA) and multifidus area and psoas muscle density (PMD) and multifidus density were measured from CT images and analyzed to lean values. Results were standardized by z-scoring. Measurement reliability was ascertained using intraclass correlation coefficient analysis (3 independent observers). Clinical data were collected from an institutional database and the hospital's patient record database. RESULTS: The study included 301 patients (89% male, mean age 74.4 years, endovascular treatment 73.1%, rupture 7.6%). Median duration of follow-up was 2.70 (interquartile range 3.54) years and mortality 31.2%. Age, female gender, and body mass index were associated with PMA, PMD, and lean psoas muscle area (LPMA). L3 left PMD, total psoas muscle density, right and left LPMA, lean total psoas muscle area (LTPMA), and L2 right LPMA and LTPMA (hazard ratio 0.74-0.78 per 1 standard deviation, P < 0.05 to P < 0.01) were independently associated with improved survival in multivariable analysis. CONCLUSIONS: L2-L3 PMD and LPMA are reliable, feasible, and independent predictors of mortality in patients treated for AAA. For every standard deviation increase in these standardized z-score muscle parameters, there was a 22%-26% decrease in the probability of death during follow-up.

Expression of activin/inhibin receptor and binding protein genes and regulation of activin/inhibin peptide secretion in human adrenocortical cells.

Activins and inhibins are glycoprotein hormones produced mainly in gonads but also in other organs. They are believed to be important para/autocrine regulators of various cell functions. We investigated activin/inhibin receptor and binding protein gene expression and the regulation of activin/inhibin secretion in human adrenal cells. RT-PCR revealed inhibin/activin alpha-, betaA/B-subunit, follistatin, activin type I/II receptor, and inhibin receptor (betaglycan and inhibin-binding protein) mRNA expression in fetal and adult adrenals and cultured adrenocortical cells. Cultured cells secreted activin A and inhibin A/B as determined by specific ELISAs. ACTH stimulated inhibin A/B secretion in fetal (1.8- and 1.8-fold of control, respectively) and in adult cells (3.4- and 1.7-fold of control, respectively) without significant effect on activin A. 8-bromoadenosine cAMP (protein kinase A activator) increased activin A and inhibin A/B secretion in the human adrenocortical NCI-H295R cell line (32-, 17-, and 3-fold of control, respectively). 12-O-tetradecanoyl phorbol-13-acetate (protein kinase C activator) stimulated both activin A and inhibin A secretion (764- and 32-fold of control, respectively), and activin treatment increased inhibin B secretion in these cells (25-fold of control). In conclusion, human adrenocortical cells produce dimeric activins and inhibins. ACTH stimulates inhibin secretion and decreases activin/inhibin secretion ratio, probably via the protein kinase A signal transduction pathway. This, together with the adrenocortical activin/ inhibin receptor and binding protein expression, suggests a physiological role for activins and inhibins in the human adrenal gland.

Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.

Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E(2), probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to activin signal transduction in human ovaries.

Preoperative white matter lesions are independent predictors of long-term survival after internal carotid endarterectomy.

BACKGROUND: Cerebral white matter lesions (WMLs) predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT) scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. METHODS: A total of 353 of 481 (73.4%) consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%), amaurosis fugax (n = 52, 14.7%), transient ischemic attack (n = 135, 38.2%) or ischemic stroke (n = 138, 39.1%), from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria) in a blinded fashion. Internal carotid artery (ICA) stenoses were angiographically graded (<50, 50-69, 70-99 and 100%). Odds ratios (ORs) and hazard ratios (HRs) are reported (ORs and HRs ≤1 indicate a beneficial effect). The median follow-up time was 67 months (interquartile range 45.5, range 0-129 months). Spearman's rho was used to estimate intraobserver agreement. Binary logistic regression was performed to analyze the association of risk factors with WMLs. Cox regression proportional hazards analysis was used to study the effect of different factors on survival. RESULTS: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p < 0.0001). Only age (OR 1.10, 95% CI 1.06-1.15; p < 0.0001 per year), degree of ipsilateral ICA stenosis (OR 2.22, 95% CI 1.08-4.55; p < 0.05 per stenosis grade) and indication category (OR 1.63, 95% CI 1.19-2.24; p < 0.01 per category) remained independently associated with WMLs. Age (HR 1.04, 95% CI 1.01-1.08; p < 0.05 per year), diabetes (HR 1.59, 95% CI 1.01-2.49; p < 0.05), peripheral arterial disease (HR 2.47, 95% CI 1.46-4.15; p < 0.01), degree of ipsilateral ICA stenosis (HR 2.56, 95% CI 1.12-5.87; p < 0.05 per stenosis grade) and WMLs (HR 3.83, 95% CI 1.17-12.5; p < 0.05) remained independently associated with increased long-term mortality. CONCLUSIONS: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells.

Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) have been shown to be involved in ovarian follicular growth/development and steroidogenesis. Recently, a number of low-affinity IGFBP-related proteins (IGFBP-rP) have been characterized. In this study, we investigated the expression of the gene for IGFBP-rP2 (also known as connective tissue growth factor, CTGF) in human granulosa cells in vitro and in vivo. Northern blot analysis demonstrated that IGFBP-rP2 mRNA is expressed in cultured human granulosa-luteal cells obtained from women undergoing an IVF programme. Accumulation of IGFBP-rP2 mRNA was dose-dependently down-regulated by FSH and LH after 24 h treatment (both P < 0.05) in cultured granulosa-luteal cells. The inhibitory effects of gonadotrophins were mimicked by treatment with the protein kinase A activator, (Bu)(2)cAMP. Protein kinase C inhibitor staurosporine reduced, whereas protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) increased, IGFBP-rP2 mRNA accumulation. These results suggest that the inhibitory effects of gonadotrophins on IGFBP-rP2 gene expression may involve signal transduction via both protein kinase A and C pathways. Immunohistochemical analysis revealed positive staining for IGFBP-rP2 in the granulosa and theca cells of normal human ovarian follicles. Corpus luteum and ovarian surface epithelial cells were also positively stained. Modulation of IGFBP-rP2 expression by gonadotrophic hormones may have a role in ovarian follicular development and in the ovulatory process.